The objectives of this proposal are: 1) to investigate and define the effectors of cyclic nucleotide and prostaglandin metabolism of human synoviocytes, 2) to determine differentiated synoviocyte function (collagen and hyaluronate synthesis, growth and phagocytosis) and its regulation by cyclic nucleotides and prostaglandins, 3) to investigate the mechanism of hormone-induced synoviocyte refractoriness and 4) to determine the effect of various normal and diseased cell products on synoviocyte responsiveness and certain differentiated functions. Synoviocyte response to effectors will be assayed by measuring intracellular cAMP by the Gilman protein binding assay and prostaglandin synthesis by isotopic assays. Differentiated function will be measured either by specific enzyme assays for prolyl hydroxylase or hyaluronic acid synthetase or by assaying total collagen and hyaluronate synthesis using isotopic methods. Refractory states will be investigated by assaying for protein kinase, PDE, phosphoprotein phosphatase and adenylate cyclase activities in normal and refractory synoviocytes.